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Article ; Online: Markers of bone metabolism in eugonadal female patients with beta-thalassemia major.

Angelopoulos, Nicholas G / Goula, Anastasia / Katounda, Eugenia / Rombopoulos, Grigorios / Kaltzidou, Victoria / Kaltsas, Dimitrios / Konstandelou, Evangellia / Tolis, George

Pediatric hematology and oncology

2007 Volume 24, Issue 7, Page(s) 481–491

Abstract: Osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) have been recently implicated in the pathogenesis of various types of osteoporosis. The aim of this study was to investigate bone turnover in eugonadal female patients with this ... ...

Abstract	Osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) have been recently implicated in the pathogenesis of various types of osteoporosis. The aim of this study was to investigate bone turnover in eugonadal female patients with this disease and characterize the possible role of the OPG/RANKL system in thalassemia-related bone loss. Markers of bone turnover and bone mineral density (BMD) were measured in 16 eugonadal young females with beta-thalassemia major and 18 age- and sex-matched healthy controls. Bone turnover was significantly increased in thalassemic patients compared to controls but OPG was significantly higher in healthy subjects. BMD values negatively correlated with urine markers of bone resorption but not with OPG/sRANKL system.
MeSH term(s)	Adult ; Amino Acids/urine ; Biomarkers/metabolism ; Bone Density ; Bone Resorption/etiology ; Bone and Bones/metabolism ; Collagen Type I/urine ; Female ; Humans ; Osteocalcin/blood ; Osteoporosis/etiology ; Osteoporosis/metabolism ; Osteoprotegerin/blood ; Peptides/urine ; Receptor Activator of Nuclear Factor-kappa B/blood ; beta-Thalassemia/blood ; beta-Thalassemia/complications ; beta-Thalassemia/metabolism
Chemical Substances	Amino Acids ; Biomarkers ; Collagen Type I ; Osteoprotegerin ; Peptides ; Receptor Activator of Nuclear Factor-kappa B ; collagen type I trimeric cross-linked peptide ; Osteocalcin (104982-03-8) ; deoxypyridinoline (90032-33-0)
Language	English
Publishing date	2007-10
Publishing country	England
Document type	Journal Article
ZDB-ID	632914-7
ISSN	1521-0669 ; 0888-0018
ISSN (online)	1521-0669
ISSN	0888-0018
DOI	10.1080/08880010701533611
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Article: Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system in patients with beta-thalassemia major.

Angelopoulos, Nicholas G / Goula, Anastasia / Katounda, Eugenia / Rombopoulos, Grigorios / Kaltzidou, Victoria / Kaltsas, Dimitrios / Malaktari, Sophia / Athanasiou, Vassilis / Tolis, George

Journal of bone and mineral metabolism

2007 Volume 25, Issue 1, Page(s) 60–67

Abstract: Osteoporosis represents an important cause of morbidity in patients with beta-thalassemia major, and its etiology is multifactorial. Thus, the aim of this study was to characterize the possible role of the osteoprotegerin (OPG) and receptor activator of ... ...

Abstract	Osteoporosis represents an important cause of morbidity in patients with beta-thalassemia major, and its etiology is multifactorial. Thus, the aim of this study was to characterize the possible role of the osteoprotegerin (OPG) and receptor activator of the NF-kappaB ligand (RANKL) system in thalassemia-related bone loss. Serum concentrations of OPG, soluble RANKL (s-RANKL), markers of bone turnover, and lumbar spine bone mineral density (BMD) were measured in random samples of males (n = 29; mean age +/- SEM, 24.26 +/- 1.29 years; range, 13-41 years) and females (n = 31; age, 24.59 +/- 0.95 years; range, 12-34 years) with beta-thalassemia major and in 30 healthy age-, height-, and weight-matched subjects. Thalassemic patients had significantly lower levels of OPG compared with controls (2.54 +/- 0.12 vs. 3.25 +/- 0.122, respectively; P < 0.05) and higher, albeit not statistically significantly, serum levels of s-RANKL (0.350 +/- 0.03 vs. 0.295 +/- 0.046, respectively; P < 0.05). s-RANKL correlated negatively with age (r = -0.3, P < 0.05), and OPG correlated positively with the duration of the interval between the onset of transfusions and chelation therapy (r = 0.52, P < 0.001). Regarding markers of bone metabolism, plasma values of osteocalcin correlated positively with s-RANKL (r = 0.40, P < 0.05) and negatively with OPG/s-RANKL ratio (r = -0.55, P < 0.01). In multiple regression analysis only cross-linked N-teleopeptide of type I collagen (NTX) significantly accounted for BMD. Although the OPG/RANKL system may have some clinical usefulness as a marker of bone turnover in beta-thalassemia, conventional markers of bone turnover more accurately represent changes in the BMD of these patients.
MeSH term(s)	Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Osteoporosis/complications ; Osteoprotegerin/blood ; Osteoprotegerin/physiology ; RANK Ligand/blood ; Receptor Activator of Nuclear Factor-kappa B/blood ; Receptor Activator of Nuclear Factor-kappa B/physiology ; beta-Thalassemia/blood ; beta-Thalassemia/complications
Chemical Substances	Osteoprotegerin ; RANK Ligand ; Receptor Activator of Nuclear Factor-kappa B ; TNFSF11 protein, human
Language	English
Publishing date	2007
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1295123-7
ISSN	1435-5604 ; 0914-8779
ISSN (online)	1435-5604
ISSN	0914-8779
DOI	10.1007/s00774-006-0728-6
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Article: Medical treatment of acromegaly: comorbidities and their reversibility by somatostatin analogs.

Tolis, George / Angelopoulos, Nicholas G / Katounda, Eugenia / Rombopoulos, Grigorios / Kaltzidou, Victoria / Kaltsas, Dimitrios / Protonotariou, Anthi / Lytras, Aristides

Neuroendocrinology

2006 Volume 83, Issue 3-4, Page(s) 249–257

Abstract: Relief of symptoms can be achieved following surgery for growth hormone (GH)-secreting adenomas, as well as after pharmacological therapy with somatostatin analogs. Recently, long-acting somatostatin analog depot formulations, octreotide LAR and ... ...

Abstract	Relief of symptoms can be achieved following surgery for growth hormone (GH)-secreting adenomas, as well as after pharmacological therapy with somatostatin analogs. Recently, long-acting somatostatin analog depot formulations, octreotide LAR and lanreotide SR have become available. Somatostatin analogs control GH/insulin-like growth factor (IGF)-1 excess, induce tumor shrinkage in a high proportion of patients, improve symptoms of acromegaly with relatively limited side effects and are successfully administered in patients not suitable for surgery. Furthermore, preoperative somatostatin analogs have been suggested to improve outcome for tumors with limited invasiveness, while surgical tumor debulking in cases that are, at least partially, somatostatin resistant, increases the achievement of normal IGF-1 levels by postoperative somatostatin analog treatment. Effective control of hypertension, as well as diabetes, is mandatory in order to reduce the increased vascular morbidity/mortality. Control of GH/IGF-1 excess generally improves glucose metabolism. Somatostatin analogs improve insulin sensitivity, exerting, however, a concomitant direct inhibitory effect on insulin secretion, with a net balance leaning towards a deterioration in glucose homeostasis. As a result, oral insulin secretagogues (and/or insulin) should probably be preferred to insulin sensitizers in acromegalic patients developing diabetes while on somatostatin analogs. Nevertheless, glucose tolerance remains normal in most of the nondiabetic acromegalic patients, while diabetic acromegalic patients on insulin are at risk for hypoglycemia during initiation of somatostatin analog therapy. Although successful management of acromegaly has been associated with improvement in morphological and functional parameters of cardiomyopathy, limited and conflicting information is available regarding the effect on blood pressure control. Contradictory results have also been reported regarding sleep hypopnea or apnea in treated acromegalic patients. As acromegalic skeletal abnormalities are rather irreversible, apneic episodes may persist after normalization of hormonal levels. Aggressive therapy, including surgery, pharmacological treatment and, in some cases, pituitary irradiation, aiming at normalization of IGF-1 levels, is required for arthropathy management. Some improvement in pain, crepitus and range of motion has been observed after treatment with somatostatin analogs. Information on the impact of disease control, either by surgery or somatostatin analog treatment, on gonadal function is limited. Finally, the link between the hormonal/biochemical and the psychiatric/psychological features of acromegaly, as well as a potential basis for positive effects of somatostatin analog therapy remain unclear.
MeSH term(s)	Acromegaly/blood ; Acromegaly/complications ; Acromegaly/drug therapy ; Acromegaly/surgery ; Adenoma/blood ; Adenoma/complications ; Adenoma/drug therapy ; Adenoma/surgery ; Antineoplastic Agents, Hormonal/therapeutic use ; Carbohydrate Metabolism/drug effects ; Carbohydrate Metabolism/physiology ; Human Growth Hormone/blood ; Humans ; Hypertension/complications ; Hypertension/drug therapy ; Hypertension/prevention & control ; Hypogonadism/complications ; Hypogonadism/drug therapy ; Hypogonadism/prevention & control ; Joint Diseases/complications ; Joint Diseases/drug therapy ; Joint Diseases/prevention & control ; Octreotide/therapeutic use ; Peptides, Cyclic/therapeutic use ; Pituitary Neoplasms/blood ; Pituitary Neoplasms/complications ; Pituitary Neoplasms/drug therapy ; Pituitary Neoplasms/surgery ; Sleep Apnea Syndromes/complications ; Sleep Apnea Syndromes/drug therapy ; Sleep Apnea Syndromes/prevention & control ; Somatostatin/analogs & derivatives ; Somatostatin/therapeutic use
Chemical Substances	Antineoplastic Agents, Hormonal ; Peptides, Cyclic ; lanreotide (0G3DE8943Y) ; Human Growth Hormone (12629-01-5) ; Somatostatin (51110-01-1) ; Octreotide (RWM8CCW8GP)
Language	English
Publishing date	2006
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	123303-8
ISSN	1423-0194 ; 0028-3835
ISSN (online)	1423-0194
ISSN	0028-3835
DOI	10.1159/000095535
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Article: Evaluation of bone mineral density of the lumbar spine in patients with beta-thalassemia major with dual-energy x-ray absorptiometry and quantitative computed tomography: a comparison study.

Angelopoulos, Nicholas G / Katounda, Eugenia / Rombopoulos, Grigorios / Goula, Anastasia / Kaltzidou, Victoria / Kaltsas, Dimitrios / Ioannis, Pappas / Tolis, George

Journal of pediatric hematology/oncology

2006 Volume 28, Issue 2, Page(s) 73–78

Abstract: Osteoporosis is a common, multifactorial cause of morbidity in patients with beta-thalassemia. The present study was performed to compare bone mineral density (BMD) results in the lumbar spine of thalassemic patients measured by both dual-energy x-ray ... ...

Abstract	Osteoporosis is a common, multifactorial cause of morbidity in patients with beta-thalassemia. The present study was performed to compare bone mineral density (BMD) results in the lumbar spine of thalassemic patients measured by both dual-energy x-ray absorptiometry (DEXA) and quantitative computed tomography (QCT), and to determine their correlations with the markers of bone turnover. BMD was measured in the lumbar spine of 13 regularly transfused patients with beta-thalassemia major by both DEXA and QCT. Blood and urine samples were obtained for the determination of biochemical and hormonal profiles. Both T-scores and Z-scores were higher when measured by QCT (T-score = -0.41 +/- 1.31, Z-score = -0.56 +/- 1.08, mean +/- SD) compared with the values given by DEXA (T-score = -2.57 +/- 0.88, Z-score = -2.32 +/- 1.11, P = 0.0005). In comparison to DEXA, QCT T-scores were more closely correlated with age (r = -0.19 vs. r = -0.70, P = 0.0068). Strong negative correlation was found between QCT values and age (r = -0.67, P = 0.01). In comparison to DEXA T-scores, QCT T-scores were more closely correlated with osteocalcin, urine N-telopeptide cross-links of type I collagen, and deoxypyridinoline, but without statistical significance. DEXA T-scores were better correlated only with urine C-terminal telopeptides of type I collagen, but again without statistical significance. These results imply that the two methods cannot be used interchangeably in assessing BMD in thalassemic patients. However, which one of these two techniques more precisely determines the overall strength of vertebrae in patients with beta-thalassemia remains to be investigated.
MeSH term(s)	Absorptiometry, Photon ; Adult ; Alkaline Phosphatase/blood ; Amino Acids/urine ; Biomarkers ; Bone Density ; Collagen/urine ; Collagen Type I ; Female ; Humans ; Lumbar Vertebrae/diagnostic imaging ; Osteocalcin/blood ; Osteoporosis/blood ; Osteoporosis/diagnostic imaging ; Osteoporosis/etiology ; Osteoporosis/urine ; Peptides/urine ; Predictive Value of Tests ; Tomography, X-Ray Computed/methods ; Transfusion Reaction ; beta-Thalassemia/complications ; beta-Thalassemia/metabolism ; beta-Thalassemia/physiopathology ; beta-Thalassemia/therapy
Chemical Substances	Amino Acids ; Biomarkers ; Collagen Type I ; Peptides ; collagen type I trimeric cross-linked peptide ; Osteocalcin (104982-03-8) ; deoxypyridinoline (90032-33-0) ; Collagen (9007-34-5) ; Alkaline Phosphatase (EC 3.1.3.1)
Language	English
Publishing date	2006-02
Publishing country	United States
Document type	Evaluation Studies ; Journal Article
ZDB-ID	1231152-2
ISSN	1536-3678 ; 1077-4114 ; 0192-8562
ISSN (online)	1536-3678
ISSN	1077-4114 ; 0192-8562
DOI	10.1097/01.mph.0000199587.76055.21
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Article: Hypoparathyroidism in transfusion-dependent patients with beta-thalassemia.

Angelopoulos, Nicholas G / Goula, Anastasia / Rombopoulos, Grigorios / Kaltzidou, Victoria / Katounda, Eugenia / Kaltsas, Dimitrios / Tolis, George

Journal of bone and mineral metabolism

2006 Volume 24, Issue 2, Page(s) 138–145

Abstract: Hypoparathyroidism is thought to be a rare consequence of iron overload seen in beta-thalassemic transfused patients. This study was conducted to determine the prevalence of hypoparathyroidism in a large number of beta-thalassemic patients, and its ... ...

Abstract	Hypoparathyroidism is thought to be a rare consequence of iron overload seen in beta-thalassemic transfused patients. This study was conducted to determine the prevalence of hypoparathyroidism in a large number of beta-thalassemic patients, and its potential correlation with the presence of other endocrinopathies caused by iron overload. Serum and urine biochemical parameters were measured in 243 thalassemic patients (136 females and 107 males) in order to determine the prevalence of hypoparathyroidism and evaluate bone turnover. The patients were divided into two groups according to the presence of hypoparathyroidism. We compared the prevalence of other endocrinopathies and disease complications in the two groups. Hypoparathyroidism was detected in 13.5% of the patients (33 subjects; 17 males and 16 females). Serum-intact parathyroid hormone, and total and ionized calcium were significantly lower, while phosphorus was significantly higher in thalassemic patients with hypoparathyroidism. The reduction in BMD was more prominent in normal thalassemic patients (Z score = -2.246 +/- 0.97) compared with those with hypoparathyroidism (Z score = -1.975 +/- 0.89), although the difference was not statistically significant. Disturbed glucose metabolism was more common in patients with hypoparathyroidism (P < 0.05). In addition, heart dysfunction was statistically more frequent in this group (odds ratio = 2.51, P < 0.05). Hypoparathyroidism is a not infrequently observed complication in thalassemic patients. Since the concentration of ferritin is not a valuable tool in the prediction of the development of hypoparathyroidism, parathyroid function should be tested periodically, particularly when other iron overload-associated complications occur.
MeSH term(s)	Adult ; Age Factors ; Biochemical Phenomena ; Biochemistry ; Blood Transfusion ; Bone Density ; Bone and Bones/metabolism ; Chelating Agents/pharmacology ; Endocrine System/metabolism ; Endocrine System/pathology ; Female ; Ferritins/metabolism ; Glucose/metabolism ; Humans ; Hypoparathyroidism/metabolism ; Hypoparathyroidism/pathology ; Iron/metabolism ; Iron Chelating Agents/pharmacology ; Male ; Middle Aged ; Models, Statistical ; Parathyroid Glands/metabolism ; Parathyroid Hormone/metabolism ; Phosphorus/metabolism ; Thalassemia/metabolism ; beta-Thalassemia/metabolism
Chemical Substances	Chelating Agents ; Iron Chelating Agents ; Parathyroid Hormone ; Phosphorus (27YLU75U4W) ; Ferritins (9007-73-2) ; Iron (E1UOL152H7) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2006
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1295123-7
ISSN	1435-5604 ; 0914-8779
ISSN (online)	1435-5604
ISSN	0914-8779
DOI	10.1007/s00774-005-0660-1
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Article ; Online: Medical Treatment of Acromegaly: Comorbidities and Their Reversibility by Somatostatin Analogs

Tolis, George / Angelopoulos, Nicholas G. / Katounda, Eugenia / Rombopoulos, Grigorios / Kaltzidou, Victoria / Kaltsas, Dimitrios / Protonotariou, Anthi / Lytras, Aristides

Neuroendocrinology - International Journal for Basic and Clinical Studies on Neuroendocrine Relationships

2006 Volume 83, Issue 3-4, Page(s) 249–257

Abstract	Relief of symptoms can be achieved following surgery for growth hormone (GH)-secreting adenomas, as well as after pharmacological therapy with somatostatin analogs. Recently, long-acting somatostatin analog depot formulations, octreotide LAR and lanreotide SR have become available. Somatostatin analogs control GH/insulin-like growth factor (IGF)-1 excess, induce tumor shrinkage in a high proportion of patients, improve symptoms of acromegaly with relatively limited side effects and are successfully administered in patients not suitable for surgery. Furthermore, preoperative somatostatin analogs have been suggested to improve outcome for tumors with limited invasiveness, while surgical tumor debulking in cases that are, at least partially, somatostatin resistant, increases the achievement of normal IGF-1 levels by postoperative somatostatin analog treatment. Effective control of hypertension, as well as diabetes, is mandatory in order to reduce the increased vascular morbidity/mortality. Control of GH/IGF-1 excess generally improves glucose metabolism. Somatostatin analogs improve insulin sensitivity, exerting, however, a concomitant direct inhibitory effect on insulin secretion, with a net balance leaning towards a deterioration in glucose homeostasis. As a result, oral insulin secretagogues (and/or insulin) should probably be preferred to insulin sensitizers in acromegalic patients developing diabetes while on somatostatin analogs. Nevertheless, glucose tolerance remains normal in most of the nondiabetic acromegalic patients, while diabetic acromegalic patients on insulin are at risk for hypoglycemia during initiation of somatostatin analog therapy. Although successful management of acromegaly has been associated with improvement in morphological and functional parameters of cardiomyopathy, limited and conflicting information is available regarding the effect on blood pressure control. Contradictory results have also been reported regarding sleep hypopnea or apnea in treated acromegalic patients. As acromegalic skeletal abnormalities are rather irreversible, apneic episodes may persist after normalization of hormonal levels. Aggressive therapy, including surgery, pharmacological treatment and, in some cases, pituitary irradiation, aiming at normalization of IGF-1 levels, is required for arthropathy management. Some improvement in pain, crepitus and range of motion has been observed after treatment with somatostatin analogs. Information on the impact of disease control, either by surgery or somatostatin analog treatment, on gonadal function is limited. Finally, the link between the hormonal/biochemical and the psychiatric/psychological features of acromegaly, as well as a potential basis for positive effects of somatostatin analog therapy remain unclear.
Keywords	Acromegaly ; Somatostatin analogs ; Diabetes ; Hypertension ; Arthropathy ; Hypogonadism ; Sleep apnea
Language	English
Publisher	S. Karger AG
Publishing place	Basel
Publishing country	Switzerland
Document type	Article ; Online
ZDB-ID	123303-8
ISSN	1423-0194 ; 0028-3835 ; 0028-3835
ISSN (online)	1423-0194
ISSN	0028-3835
DOI	10.1159/000095535
Database	Karger publisher's database

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Article: Medical Treatment of Acromegaly: Comorbidities and Their Reversibility by Somatostatin Analogs

Tolis, George / Angelopoulos, Nicholas G. / Katounda, Eugenia / Rombopoulos, Grigorios / Kaltzidou, Victoria / Kaltsas, Dimitrios / Protonotariou, Anthi / Lytras, Aristides

Neuroendocrinology

2006 Volume 83, Issue 3-4, Page(s) 249–257

Institution	Division of Endocrinology and Metabolism, Hippokrateion General Hospital, Athens, Greece
Abstract	Relief of symptoms can be achieved following surgery for growth hormone (GH)-secreting adenomas, as well as after pharmacological therapy with somatostatin analogs. Recently, long-acting somatostatin analog depot formulations, octreotide LAR and lanreotide SR have become available. Somatostatin analogs control GH/insulin-like growth factor (IGF)-1 excess, induce tumor shrinkage in a high proportion of patients, improve symptoms of acromegaly with relatively limited side effects and are successfully administered in patients not suitable for surgery. Furthermore, preoperative somatostatin analogs have been suggested to improve outcome for tumors with limited invasiveness, while surgical tumor debulking in cases that are, at least partially, somatostatin resistant, increases the achievement of normal IGF-1 levels by postoperative somatostatin analog treatment. Effective control of hypertension, as well as diabetes, is mandatory in order to reduce the increased vascular morbidity/mortality. Control of GH/IGF-1 excess generally improves glucose metabolism. Somatostatin analogs improve insulin sensitivity, exerting, however, a concomitant direct inhibitory effect on insulin secretion, with a net balance leaning towards a deterioration in glucose homeostasis. As a result, oral insulin secretagogues (and/or insulin) should probably be preferred to insulin sensitizers in acromegalic patients developing diabetes while on somatostatin analogs. Nevertheless, glucose tolerance remains normal in most of the nondiabetic acromegalic patients, while diabetic acromegalic patients on insulin are at risk for hypoglycemia during initiation of somatostatin analog therapy. Although successful management of acromegaly has been associated with improvement in morphological and functional parameters of cardiomyopathy, limited and conflicting information is available regarding the effect on blood pressure control. Contradictory results have also been reported regarding sleep hypopnea or apnea in treated acromegalic patients. As acromegalic skeletal abnormalities are rather irreversible, apneic episodes may persist after normalization of hormonal levels. Aggressive therapy, including surgery, pharmacological treatment and, in some cases, pituitary irradiation, aiming at normalization of IGF-1 levels, is required for arthropathy management. Some improvement in pain, crepitus and range of motion has been observed after treatment with somatostatin analogs. Information on the impact of disease control, either by surgery or somatostatin analog treatment, on gonadal function is limited. Finally, the link between the hormonal/biochemical and the psychiatric/psychological features of acromegaly, as well as a potential basis for positive effects of somatostatin analog therapy remain unclear.
Keywords	Acromegaly ; Somatostatin analogs ; Diabetes ; Hypertension ; Arthropathy ; Hypogonadism ; Sleep apnea
Language	English
Publishing date	2006-10-16
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Reviews
ZDB-ID	123303-8
ISBN	978-3-8055-8198-1 ; 978-3-318-01414-3 ; 3-8055-8198-X ; 3-318-01414-1
ISSN	1423-0194 ; 0028-3835
ISSN (online)	1423-0194
ISSN	0028-3835
DOI	10.1159/000095535
Database	Karger publisher's database

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